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A Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03367403
Collaborator
(none)
272
Enrollment
61
Locations
3
Arms
45.1
Actual Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of LY3002813 in early symptomatic Alzheimer's disease.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
272 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Assessment of Safety, Tolerability and Efficacy of LY3002813 in Early Symptomatic Alzheimer's Disease
Actual Study Start Date :
Dec 18, 2017
Actual Primary Completion Date :
Dec 4, 2020
Actual Study Completion Date :
Sep 21, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Donanemab Monotherapy (Donanemab-M)

Participants received 700 milligram (mg) donanemab intravenously (IV) every 4 weeks (Q4W) x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks.

Drug: Donanemab
Administered IV
Other Names:
  • LY3002813

    		•
    Placebo Comparator: Placebo

    Participants received placebo IV Q4W for up to 72 weeks.

    Drug: Placebo
    Administered IV
    Experimental: Donanemab in Combination With LY3202626 (Donanemab-C)

    Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks. As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline.

    Drug: Donanemab
    Administered IV
    Other Names:
  • LY3002813

    • Drug: LY3202626
    Administered orally

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score [Baseline, 76 Weeks]

      Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, acetylcholinesterase inhibitor (AChEI) and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Secondary Outcome Measures

    1. Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score [Baseline, 76 Weeks]

      The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS--Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    2. Change From Baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score [Baseline, 76 Weeks]

      CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    3. Change From Baseline in the Mini Mental State Examination (MMSE) Score [Baseline, 76 Weeks]

      MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    4. Change From Baseline in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score [Baseline, 76 Weeks]

      The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    5. Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan [Baseline, 76 Weeks]

      Florbetapir PET imaging was used as a quantitative amyloid biomarker. Florbetapir PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. Least Squares mean change was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    6. Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan [Baseline, 76 Weeks]

      Flortaucipir PET imaging was used as a quantitative tau biomarker. Flortaucipir PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using two measures: weighted average Standardized Uptake Value Ratio (MUBADA SUVR) in the brain relative to the cerebellum gray as a reference region and the global tau load (TauL) generated using a TauIQ method. Larger weighted average SUVR reflects the larger cortical tau burden relative to cerebellum gray. The TauIQ method quantifies the spatiotemporal accumulation pattern of tau and larger TauL value reflects the larger global tau level in the brain as determined using a TauIQ mathematical framework. Least Squares mean change was controlled for baseline + age + treatment (Type III sum of squares).

    7. Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) [Baseline, 76 Weeks]

      MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain atrophy. Volumetric MRI (vMRI) parameters were measured in 14 brain regions: bilateral cortical, bilateral entorhinal cortex, bilateral hippocampus, bilateral inferior parietal lobe, bilateral isthmus cingulate, bilateral lateral parietal lobe, bilateral medial temporal lobe, bilateral precuneus, bilateral prefrontal lobe, bilateral superior temporal lobe, bilateral ventricles, bilateral whole brain, bilateral whole temporal lobe, and bilateral white matter. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, fixed covariates of baseline, and age at baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months.

    • MMSE score of 20 to 28 (inclusive) at baseline or an acceptable historical flortaucipir PET scan within 6 months prior to baseline that meets the central read criteria.

    • Meet 18F flortaucipir PET scan eligibility criteria.

    • Meet 18F florbetapir PET scan (central read) eligibility criteria.

    Exclusion Criteria:

    • Have a history of long QT syndrome.

    • Have received treatment with a stable dose of an acetylcholinesterase inhibitor (AChEI) and/or memantine for less than 2 months before randomization.

    • Contraindication to MRI.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    2 Banner Sun Health Research Institute Sun City Arizona United States 85351
    3 Neurology Center of North Orange County Fullerton California United States 92835
    4 Irvine Clinical Research Center Irvine California United States 92614
    5 Institute for Memory Impairment & Neurological Disorders Irvine California United States 92697
    6 Pharmacology Research Institute Newport Beach California United States 92660
    7 Pacific Research Network Inc San Diego California United States 92103
    8 Sharp Mesa Vista Hospital San Diego California United States 92123
    9 Syrentis Clinical Research Santa Ana California United States 92705
    10 Associated Neurologists, PC - Danbury Danbury Connecticut United States 06810
    11 KI Health Partners, LLC d/b/a NE Inst. for Clin. Res. Stamford Connecticut United States 06905
    12 JEM Research Institute Atlantis Florida United States 33462
    13 Bradenton Research Center Bradenton Florida United States 34205
    14 Brain Matters Research Delray Beach Florida United States 33445
    15 Infinity Clinical Research, LLC Hollywood Florida United States 33021
    16 Jacksonville Center for Clinical Research Jacksonville Florida United States 32216
    17 Merritt Island Medical Research LLC Merritt Island Florida United States 32592
    18 Pharmax Research Clinic Miami Florida United States 33126
    19 Miami Jewish Health Systems Miami Florida United States 33137
    20 Suncoast Clinical Research New Port Richey Florida United States 34652
    21 Compass Research Orlando Florida United States 32806
    22 Palm Beach Neurological Group Palm Beach Gardens Florida United States 33410
    23 Quantum Laboratories Pompano Beach Florida United States 33064
    24 Progressive Medical Research Port Orange Florida United States 32127
    25 Intercoastal Medical Group Sarasota Florida United States 34239
    26 Axiom Research Tampa Florida United States 33609
    27 Stedman Clinical Trials Tampa Florida United States 33613
    28 Compass Research The Villages Florida United States 32162
    29 Great Lakes Clinical Trials Chicago Illinois United States 60640
    30 Alexian Brothers Medical Center Elk Grove Village Illinois United States 60007
    31 Indiana University School of Medicine Indianapolis Indiana United States 46202
    32 Josephson Wallack Munshower Neurology Indianapolis Indiana United States 46256
    33 University of Kansas Hospital Fairway Kansas United States 66160
    34 Cotton O'Neil Clinic Topeka Kansas United States 66606
    35 McLean Hospital Belmont Massachusetts United States 02478
    36 ActivMed Practices & Research, Inc Methuen Massachusetts United States 01844
    37 Boston Center for Memory Newton Massachusetts United States 02459
    38 Donald S Marks Plymouth Massachusetts United States 02360-4843
    39 Washington University Saint Louis Missouri United States 63108
    40 Las Vegas Medical Research Las Vegas Nevada United States 89113
    41 Advanced Memory Research Institute of New Jersey Toms River New Jersey United States 08755
    42 Behavioral Health Center Research Charlotte North Carolina United States 28211
    43 Guilford Neurologic Associates Greensboro North Carolina United States 27405
    44 Raleigh Neurology Associates Raleigh North Carolina United States 27607
    45 Piedmont Medical Research Winston-Salem North Carolina United States 27103
    46 Insight Clinical Trials Beachwood Ohio United States 44122
    47 Ohio State University Medical Center Columbus Ohio United States 43210
    48 Neurology Diagnostics, Inc. Dayton Ohio United States 45459
    49 Abington Neurological Associates Willow Grove Pennsylvania United States 19090
    50 Rhode Island Hospital Providence Rhode Island United States 02903
    51 Butler Hospital Providence Rhode Island United States 02906
    52 Texas Neurology, PA Dallas Texas United States 75214
    53 Houston Methodist Houston Texas United States 77030
    54 The Memory Clinic Bennington Vermont United States 05201
    55 Cognition Health Fairfax Virginia United States 22031
    56 National Clinical Research - Richmond Richmond Virginia United States 23294
    57 Bruyere Research Institute Ottawa Ontario Canada K1N 5C8
    58 Kawartha Regional Memory Clinic Peterborough Ontario Canada K9H2P4
    59 Toronto Memory Program Toronto Ontario Canada M3B2S7
    60 Clinique de la Memoire de l'Outaouais Gatineau Quebec Canada J8T 8J1
    61 DIEX Recherche Sherbrooke, Inc Sherbrooke Quebec Canada J1L 0H8

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03367403
    Other Study ID Numbers:
    • 16933
    • I5T-MC-AACG
    First Posted:
    Dec 8, 2017
    Last Update Posted:
    Feb 15, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Eli Lilly and Company
    TRAILBLAZER-ALZ
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    Participant Flow

    Recruitment Details As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline. Thus, the arm was not utilized, and no data collected for outcomes; only safety data reported.
    Pre-assignment Detail
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C)
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks. Participants received 700 milligram (mg) donanemab intravenously (IV) every 4 weeks (Q4W) x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks.
    Period Title: Overall Study
    STARTED 131 126 15
    Received at Least One Dose of Study Drug 131 125 15
    COMPLETED 94 93 12
    NOT COMPLETED 37 33 3

    Baseline Characteristics

    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C) Total
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks. Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks. Total of all reporting groups
    Overall Participants 131 126 15 272
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    74.95
    (5.58)
    75.35
    (5.43)
    75.20
    (5.99)
    75.15
    (5.52)
    Sex: Female, Male (Count of Participants)
    Female
    68
    51.9%
    65
    51.6%
    12
    80%
    145
    53.3%
    Male
    63
    48.1%
    61
    48.4%
    3
    20%
    127
    46.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    3.8%
    3
    2.4%
    1
    6.7%
    9
    3.3%
    Not Hispanic or Latino
    126
    96.2%
    123
    97.6%
    14
    93.3%
    263
    96.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    1.5%
    0
    0%
    0
    0%
    2
    0.7%
    Asian
    1
    0.8%
    2
    1.6%
    0
    0%
    3
    1.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    5
    3.8%
    3
    2.4%
    0
    0%
    8
    2.9%
    White
    122
    93.1%
    121
    96%
    15
    100%
    258
    94.9%
    More than one race
    1
    0.8%
    0
    0%
    0
    0%
    1
    0.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Canada
    10
    7.6%
    11
    8.7%
    0
    0%
    21
    7.7%
    United States
    121
    92.4%
    115
    91.3%
    15
    100%
    251
    92.3%
    Integrated Alzheimer's Disease Rating Scale (iADRS) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    106.20
    (13.03)
    105.88
    (13.22)
    108.93
    (10.17)
    106.20
    (12.96)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
    Description Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, acetylcholinesterase inhibitor (AChEI) and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All participants randomized to donanemab monotherapy or placebo with a baseline and at least one non-missing postbaseline iADRS data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 93 91
    Least Squares Mean (Standard Error) [score on a scale]
    -6.86
    (1.135)
    -10.06
    (1.141)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.042
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.20
    Confidence Interval (2-Sided) 95%
    0.12 to 6.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.560
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score
    Description The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS--Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with baseline and post-baseline ADAS-Cog13 data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 93 93
    Least Squares Mean (Standard Error) [score on a scale]
    2.91
    (0.659)
    4.77
    (0.660)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.040
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.86
    Confidence Interval (2-Sided) 95%
    -3.63 to -0.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.898
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score
    Description CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with baseline and post-baseline CDR-SB data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 93 90
    Least Squares Mean (Standard Error) [score on a scale]
    1.22
    (0.176)
    1.58
    (0.178)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.139
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.36
    Confidence Interval (2-Sided) 95%
    -0.83 to 0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.239
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in the Mini Mental State Examination (MMSE) Score
    Description MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with baseline and post-baseline MMSE data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg Donanemab IV Q4W x 3 doses, then 1400 mg Donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 91 90
    Least Squares Mean (Standard Error) [score on a scale]
    -2.35
    (0.386)
    -2.98
    (0.390)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.227
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.64
    Confidence Interval (2-Sided) 95%
    -0.40 to 1.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.525
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score
    Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with baseline and post-baseline ADCS-iADL data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 93 91
    Least Squares Mean (Standard Error) [score on a scale]
    -3.98
    (0.738)
    -5.20
    (0.743)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.230
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.21
    Confidence Interval (2-Sided) 95%
    -0.77 to 3.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.009
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan
    Description Florbetapir PET imaging was used as a quantitative amyloid biomarker. Florbetapir PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. Least Squares mean change was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with baseline and post-baseline PET amyloid data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 90 91
    Least Squares Mean (Standard Error) [centiloids]
    -84.13
    (2.723)
    0.93
    (2.739)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -85.06
    Confidence Interval (2-Sided) 95%
    -92.68 to -77.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.867
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan
    Description Flortaucipir PET imaging was used as a quantitative tau biomarker. Flortaucipir PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using two measures: weighted average Standardized Uptake Value Ratio (MUBADA SUVR) in the brain relative to the cerebellum gray as a reference region and the global tau load (TauL) generated using a TauIQ method. Larger weighted average SUVR reflects the larger cortical tau burden relative to cerebellum gray. The TauIQ method quantifies the spatiotemporal accumulation pattern of tau and larger TauL value reflects the larger global tau level in the brain as determined using a TauIQ mathematical framework. Least Squares mean change was controlled for baseline + age + treatment (Type III sum of squares).
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with non-missing baseline and at least one non-missing post-baseline PET tau data. Per protocol, outcomes were analyzed by comparing donanemab Monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 90 87
    Tau-IQ
    0.55
    (0.007)
    0.55
    (0.007)
    MUBADA-Cerebellum
    1.54
    (0.009)
    1.58
    (0.010)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Tau-IQ
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.560
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.01 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments MUBADA-Cerebellum
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.035
    Confidence Interval (2-Sided) 95%
    0.007 to 0.062
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)
    Description MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain atrophy. Volumetric MRI (vMRI) parameters were measured in 14 brain regions: bilateral cortical, bilateral entorhinal cortex, bilateral hippocampus, bilateral inferior parietal lobe, bilateral isthmus cingulate, bilateral lateral parietal lobe, bilateral medial temporal lobe, bilateral precuneus, bilateral prefrontal lobe, bilateral superior temporal lobe, bilateral ventricles, bilateral whole brain, bilateral whole temporal lobe, and bilateral white matter. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, fixed covariates of baseline, and age at baseline.
    Time Frame Baseline, 76 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value. Per protocol, outcomes were analyzed by comparing donanemab monotherapy (Donanemab-M) and placebo.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks.
    Measure Participants 82 83
    Bilateral Cortical
    -11.18
    (0.447)
    -8.51
    (0.445)
    Bilateral Entorhinal Cortex
    -0.17
    (0.008)
    -0.17
    (0.008)
    Bilateral Hippocampus
    -0.22
    (0.013)
    -0.22
    (0.013)
    Bilateral Inferior Parietal Lobe
    -0.53
    (0.033)
    -0.45
    (0.033)
    Bilateral Isthmuscingulate
    -0.15
    (0.008)
    -0.13
    (0.008)
    Bilateral Lateral Parietal Lobe
    -1.60
    (0.084)
    -1.26
    (0.083)
    Bilateral Medial Temporal Lobe
    -0.73
    (0.025)
    -0.72
    (0.025)
    Bilateral Precuneus
    -0.71
    (0.032)
    -0.55
    (0.032)
    Bilateral Prefrontal Lobe
    -1.50
    (0.081)
    -1.11
    (0.080)
    Bilateral Superior Temporal Lobe
    -0.73
    (0.031)
    -0.52
    (0.031)
    Bilateral Ventricles
    8.66
    (0.412)
    6.38
    (0.410)
    Bilateral Whole Brain
    -24.53
    (1.077)
    -19.95
    (1.072)
    Bilateral Whole Temporal Lobe
    -3.52
    (0.126)
    -2.84
    (0.126)
    Bilateral White Matter
    -11.03
    (0.700)
    -8.75
    (0.696)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Cortical
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.67
    Confidence Interval (2-Sided) 95%
    -3.92 to -1.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.631
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Entorhinal Cortex
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.916
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.00
    Confidence Interval (2-Sided) 95%
    -0.02 to 0.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.011
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments
    Type of Statistical Test Superiority
    Comments Bilateral Hippocampus
    Statistical Test of Hypothesis p-Value 0.771
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.03 to 0.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.019
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Inferior Parietal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.094
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.08
    Confidence Interval (2-Sided) 95%
    -0.17 to 0.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.047
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Isthmuscingulate
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.052
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.04 to 0.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.011
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Lateral Parietal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -0.57 to -0.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.118
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Medial Temporal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.731
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.08 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.036
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Precuneus
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.16
    Confidence Interval (2-Sided) 95%
    -0.25 to -0.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.046
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Prefrontal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.62 to -0.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.114
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Superior Temporal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.21
    Confidence Interval (2-Sided) 95%
    -0.30 to -0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.044
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Ventricles
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.28
    Confidence Interval (2-Sided) 95%
    1.14 to 3.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.581
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Whole Brain
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.58
    Confidence Interval (2-Sided) 95%
    -7.58 to -1.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.519
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral Whole Temporal Lobe
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.68
    Confidence Interval (2-Sided) 95%
    -1.03 to -0.33
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.178
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Donanemab Monotherapy (Donanemab-M), Placebo
    Comments Bilateral White Matter
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -4.23 to -0.33
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.987
    Estimation Comments

    Adverse Events

    Time Frame Baseline Up To 124 Weeks
    Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
    Arm/Group Title Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C)
    Arm/Group Description Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks. Participants received placebo IV Q4W for up to 72 weeks. Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks.
    All Cause Mortality
    Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/131 (0.8%) 2/125 (1.6%) 0/15 (0%)
    Serious Adverse Events
    Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/131 (18.3%) 24/125 (19.2%) 3/15 (20%)
    Blood and lymphatic system disorders
    Anaemia 1/131 (0.8%) 2 0/125 (0%) 0 0/15 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Atrial fibrillation 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Atrioventricular block complete 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cardiac arrest 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Sinus node dysfunction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Mouth swelling 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Nausea 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Small intestinal obstruction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    General disorders
    Asthenia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Non-cardiac chest pain 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Infections and infestations
    Bacterial sepsis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Clostridium difficile colitis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Gastroenteritis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Pneumonia 5/131 (3.8%) 5 1/125 (0.8%) 1 0/15 (0%) 0
    Staphylococcal infection 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Urinary tract infection 0/131 (0%) 0 1/125 (0.8%) 1 1/15 (6.7%) 1
    Urosepsis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Injury, poisoning and procedural complications
    Extradural haematoma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Fall 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hip fracture 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Humerus fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Infusion related reaction 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Pelvic fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Road traffic accident 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Seroma 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Subdural haematoma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Upper limb fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 2/131 (1.5%) 2 1/125 (0.8%) 2 1/15 (6.7%) 1
    Diabetes mellitus 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Gout 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Type 2 diabetes mellitus 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Musculoskeletal and connective tissue disorders
    Intervertebral disc degeneration 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Osteoarthritis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Rheumatoid arthritis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder squamous cell carcinoma stage ii 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Breast cancer 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Non-small cell lung cancer stage ii 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Squamous cell carcinoma of skin 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Nervous system disorders
    Amyloid related imaging abnormality-oedema/effusion 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Cerebrovascular accident 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cognitive disorder 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Dizziness 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Encephalopathy 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Motor neurone disease 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Subarachnoid haemorrhage 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Syncope 2/131 (1.5%) 2 1/125 (0.8%) 1 0/15 (0%) 0
    Psychiatric disorders
    Agitation 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Anxiety 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Brief psychotic disorder without marked stressors 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Confusional state 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Mental disorder due to a general medical condition 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Psychotic disorder 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Pharyngeal swelling 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Pneumonia aspiration 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Pulmonary embolism 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Skin and subcutaneous tissue disorders
    Drug eruption 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Vascular disorders
    Aortic aneurysm 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hypertension 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hypotension 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Orthostatic hypertension 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Other (Not Including Serious) Adverse Events
    Donanemab Monotherapy (Donanemab-M) Placebo Donanemab in Combination With LY3202626 (Donanemab-C)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 118/131 (90.1%) 112/125 (89.6%) 15/15 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Anaemia of chronic disease 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Leukopenia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Neutropenia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Thrombocytopenia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Cardiac disorders
    Angina pectoris 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Aortic valve stenosis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Atrial fibrillation 2/131 (1.5%) 2 3/125 (2.4%) 3 0/15 (0%) 0
    Atrial flutter 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Bradycardia 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Bundle branch block left 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Bundle branch block right 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Cardiac failure congestive 0/131 (0%) 0 1/125 (0.8%) 3 0/15 (0%) 0
    Chronic left ventricular failure 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Diastolic dysfunction 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Mitral valve incompetence 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Palpitations 2/131 (1.5%) 3 1/125 (0.8%) 1 0/15 (0%) 0
    Right ventricular enlargement 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Sinus arrest 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Sinus arrhythmia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Sinus bradycardia 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Tachycardia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ventricular extrasystoles 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Congenital, familial and genetic disorders
    Arteriovenous malformation 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ear and labyrinth disorders
    Cerumen impaction 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Hypoacusis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Tinnitus 2/131 (1.5%) 2 3/125 (2.4%) 3 0/15 (0%) 0
    Vertigo 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Endocrine disorders
    Goitre 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hypothyroidism 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Eye disorders
    Cataract 4/131 (3.1%) 6 0/125 (0%) 0 0/15 (0%) 0
    Conjunctival haemorrhage 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Corneal erosion 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Dry age-related macular degeneration 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Dry eye 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Eye pain 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Eye pruritus 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Eyelid ptosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Glaucoma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Lacrimation increased 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ocular hyperaemia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Optic disc haemorrhage 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Photophobia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Photopsia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Retinal artery occlusion 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Retinal detachment 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Visual impairment 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Vitreous degeneration 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Abdominal pain 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Anal incontinence 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ascites 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Chapped lips 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Colitis ischaemic 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Constipation 2/131 (1.5%) 2 3/125 (2.4%) 3 1/15 (6.7%) 1
    Dental caries 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Diarrhoea 11/131 (8.4%) 14 5/125 (4%) 5 0/15 (0%) 0
    Dry mouth 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Dysphagia 3/131 (2.3%) 3 1/125 (0.8%) 1 0/15 (0%) 0
    Enterocolitis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Faeces soft 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Gastrooesophageal reflux disease 2/131 (1.5%) 2 3/125 (2.4%) 3 0/15 (0%) 0
    Haematemesis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Haematochezia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hiatus hernia 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Large intestine polyp 0/131 (0%) 0 2/125 (1.6%) 2 1/15 (6.7%) 1
    Melaena 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Mouth swelling 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Nausea 14/131 (10.7%) 14 4/125 (3.2%) 4 0/15 (0%) 0
    Stomatitis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Toothache 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Vomiting 7/131 (5.3%) 8 3/125 (2.4%) 3 0/15 (0%) 0
    General disorders
    Adverse drug reaction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Asthenia 4/131 (3.1%) 4 2/125 (1.6%) 2 1/15 (6.7%) 1
    Chest discomfort 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Chest pain 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Chills 1/131 (0.8%) 1 0/125 (0%) 0 1/15 (6.7%) 1
    Early satiety 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Face oedema 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Fatigue 5/131 (3.8%) 6 5/125 (4%) 5 1/15 (6.7%) 1
    Feeling abnormal 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Gait disturbance 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    General physical health deterioration 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hyperthermia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Influenza like illness 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Infusion site pain 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Infusion site swelling 0/131 (0%) 0 1/125 (0.8%) 2 0/15 (0%) 0
    Injection site pain 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Injection site pruritus 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Malaise 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Medical device site reaction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Oedema peripheral 0/131 (0%) 0 3/125 (2.4%) 3 0/15 (0%) 0
    Peripheral swelling 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Precancerous condition 0/131 (0%) 0 1/125 (0.8%) 2 0/15 (0%) 0
    Pyrexia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Soft tissue inflammation 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Systemic inflammatory response syndrome 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Vessel puncture site bruise 0/131 (0%) 0 2/125 (1.6%) 3 0/15 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cholecystitis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cholelithiasis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Immune system disorders
    Drug hypersensitivity 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Hypersensitivity 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Seasonal allergy 1/131 (0.8%) 1 0/125 (0%) 0 1/15 (6.7%) 1
    Infections and infestations
    Acute sinusitis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Asymptomatic covid-19 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Bronchitis 4/131 (3.1%) 4 1/125 (0.8%) 1 0/15 (0%) 0
    Bronchitis viral 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cellulitis 2/131 (1.5%) 2 2/125 (1.6%) 2 2/15 (13.3%) 2
    Clostridium difficile colitis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Conjunctivitis 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Covid-19 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Eyelid infection 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Fungal infection 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Fungal skin infection 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Gastroenteritis 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Gastrointestinal viral infection 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Gingivitis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Herpes zoster 0/131 (0%) 0 3/125 (2.4%) 3 1/15 (6.7%) 1
    Hordeolum 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Influenza 2/131 (1.5%) 2 1/125 (0.8%) 1 0/15 (0%) 0
    Labyrinthitis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Laryngitis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Localised infection 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Lower respiratory tract infection 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Lyme disease 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Nasopharyngitis 6/131 (4.6%) 7 6/125 (4.8%) 7 0/15 (0%) 0
    Onychomycosis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Oral herpes 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Otitis media acute 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Pneumonia 3/131 (2.3%) 3 4/125 (3.2%) 4 1/15 (6.7%) 1
    Postoperative wound infection 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Root canal infection 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Sinusitis 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Skin candida 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Skin infection 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Testicular abscess 0/63 (0%) 0 1/61 (1.6%) 1 0/3 (0%) 0
    Tooth abscess 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Tooth infection 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Upper respiratory tract infection 9/131 (6.9%) 11 9/125 (7.2%) 10 2/15 (13.3%) 2
    Urinary tract infection 13/131 (9.9%) 21 4/125 (3.2%) 5 2/15 (13.3%) 2
    Viral upper respiratory tract infection 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Injury, poisoning and procedural complications
    Animal bite 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Arthropod bite 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Arthropod sting 2/131 (1.5%) 3 1/125 (0.8%) 1 0/15 (0%) 0
    Bone contusion 2/131 (1.5%) 2 1/125 (0.8%) 1 0/15 (0%) 0
    Buttock injury 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cataract operation complication 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Clavicle fracture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Contusion 0/131 (0%) 0 11/125 (8.8%) 12 0/15 (0%) 0
    Eye contusion 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Facial bones fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Fall 18/131 (13.7%) 21 19/125 (15.2%) 27 1/15 (6.7%) 1
    Foot fracture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hand fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Head injury 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Infusion related reaction 8/131 (6.1%) 29 0/125 (0%) 0 1/15 (6.7%) 3
    Joint injury 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Ligament sprain 1/131 (0.8%) 1 4/125 (3.2%) 5 1/15 (6.7%) 1
    Lumbar vertebral fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Meniscus injury 1/131 (0.8%) 1 1/125 (0.8%) 1 1/15 (6.7%) 1
    Muscle strain 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Procedural pain 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Radiation injury 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Radius fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Rib fracture 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Road traffic accident 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Skin abrasion 4/131 (3.1%) 4 3/125 (2.4%) 4 1/15 (6.7%) 1
    Skin injury 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Skin laceration 2/131 (1.5%) 2 4/125 (3.2%) 4 0/15 (0%) 0
    Spinal compression fracture 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Synovial rupture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Tendon rupture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Tooth fracture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Traumatic haematoma 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Wound 2/131 (1.5%) 2 1/125 (0.8%) 2 0/15 (0%) 0
    Wrist fracture 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Aspartate aminotransferase increased 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Bacterial test positive 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Biopsy skin 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Blood alkaline phosphatase increased 0/131 (0%) 0 1/125 (0.8%) 2 0/15 (0%) 0
    Blood creatine phosphokinase increased 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Blood glucose increased 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Blood potassium decreased 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Blood pressure increased 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Blood pressure systolic increased 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    C-reactive protein increased 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cardiac murmur 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Creatinine renal clearance decreased 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Electrocardiogram pr shortened 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Electrocardiogram qt prolonged 2/131 (1.5%) 3 0/125 (0%) 0 0/15 (0%) 0
    Haemoglobin decreased 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Heart rate irregular 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Liver function test increased 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Lymphocyte morphology abnormal 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Occult blood positive 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Platelet count decreased 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Prostatic specific antigen increased 1/63 (1.6%) 1 0/61 (0%) 0 0/3 (0%) 0
    Qrs axis abnormal 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Urine leukocyte esterase positive 1/131 (0.8%) 1 0/125 (0%) 0 1/15 (6.7%) 1
    Weight decreased 4/131 (3.1%) 4 4/125 (3.2%) 4 0/15 (0%) 0
    Weight increased 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 2/131 (1.5%) 2 2/125 (1.6%) 2 0/15 (0%) 0
    Dehydration 2/131 (1.5%) 2 4/125 (3.2%) 4 0/15 (0%) 0
    Glucose tolerance impaired 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Gout 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Hypercholesterolaemia 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Hyperglycaemia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hyperkalaemia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hyperuricaemia 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Hypocalcaemia 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Hypoglycaemia 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Hypokalaemia 0/131 (0%) 0 5/125 (4%) 6 0/15 (0%) 0
    Hypomagnesaemia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hyponatraemia 2/131 (1.5%) 2 2/125 (1.6%) 2 0/15 (0%) 0
    Lactic acidosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Malnutrition 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Overweight 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Type 2 diabetes mellitus 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Vitamin b12 deficiency 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/131 (7.6%) 12 10/125 (8%) 10 3/15 (20%) 3
    Arthritis 2/131 (1.5%) 3 2/125 (1.6%) 2 0/15 (0%) 0
    Back pain 4/131 (3.1%) 5 4/125 (3.2%) 4 1/15 (6.7%) 1
    Bursitis 2/131 (1.5%) 2 2/125 (1.6%) 3 0/15 (0%) 0
    Coccydynia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Facet joint syndrome 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Intervertebral disc protrusion 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Jaw disorder 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Joint effusion 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Joint stiffness 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Joint swelling 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Mucoid degeneration of the anterior cruciate ligament 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Muscle atrophy 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Muscle spasms 1/131 (0.8%) 1 2/125 (1.6%) 3 0/15 (0%) 0
    Muscle twitching 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Muscular weakness 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Musculoskeletal chest pain 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Musculoskeletal pain 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Neck pain 1/131 (0.8%) 1 3/125 (2.4%) 3 0/15 (0%) 0
    Osteoarthritis 2/131 (1.5%) 2 1/125 (0.8%) 1 0/15 (0%) 0
    Osteochondritis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Pain in extremity 4/131 (3.1%) 4 2/125 (1.6%) 2 1/15 (6.7%) 1
    Plantar fasciitis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Rheumatoid arthritis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Rotator cuff syndrome 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Sacroiliitis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Spinal osteoarthritis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Spinal stenosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Synovial cyst 1/131 (0.8%) 2 1/125 (0.8%) 1 0/15 (0%) 0
    Temporomandibular joint syndrome 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Tendonitis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Trigger finger 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Atypical fibroxanthoma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Basal cell carcinoma 3/131 (2.3%) 3 4/125 (3.2%) 4 0/15 (0%) 0
    Benign lung neoplasm 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Bowen's disease 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Dysplastic naevus 1/131 (0.8%) 2 0/125 (0%) 0 0/15 (0%) 0
    Enchondromatosis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Keratoacanthoma 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Lip neoplasm 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Lung adenocarcinoma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Malignant melanoma 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Neuroma 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Non-hodgkin's lymphoma 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Seborrhoeic keratosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Skin papilloma 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Squamous cell carcinoma 3/131 (2.3%) 3 1/125 (0.8%) 1 0/15 (0%) 0
    Squamous cell carcinoma of skin 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Nervous system disorders
    Ageusia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits 11/131 (8.4%) 14 4/125 (3.2%) 5 1/15 (6.7%) 1
    Amyloid related imaging abnormality-oedema/effusion 33/131 (25.2%) 43 1/125 (0.8%) 2 4/15 (26.7%) 4
    Balance disorder 1/131 (0.8%) 1 2/125 (1.6%) 3 1/15 (6.7%) 1
    Burning sensation 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cerebellar microhaemorrhage 2/131 (1.5%) 4 0/125 (0%) 0 0/15 (0%) 0
    Cerebral infarction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cerebral microhaemorrhage 10/131 (7.6%) 18 3/125 (2.4%) 6 2/15 (13.3%) 2
    Cerebrovascular accident 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Cluster headache 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cognitive disorder 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Dementia alzheimer's type 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Dizziness 11/131 (8.4%) 16 14/125 (11.2%) 16 4/15 (26.7%) 4
    Dizziness postural 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Drug withdrawal headache 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Dysarthria 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Encephalopathy 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Essential tremor 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Gliosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Head discomfort 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Headache 10/131 (7.6%) 11 15/125 (12%) 17 0/15 (0%) 0
    Hemiparesis 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Hypoaesthesia 0/131 (0%) 0 2/125 (1.6%) 2 1/15 (6.7%) 1
    Intraventricular haemorrhage 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Lacunar infarction 0/131 (0%) 0 2/125 (1.6%) 3 0/15 (0%) 0
    Lethargy 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Memory impairment 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Migraine 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Neuralgia 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Neuropathy peripheral 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Occipital neuralgia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Paraesthesia 1/131 (0.8%) 1 0/125 (0%) 0 2/15 (13.3%) 2
    Parkinson's disease 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Patient elopement 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Peripheral sensorimotor neuropathy 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Polyneuropathy 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Presyncope 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Resting tremor 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Sciatica 1/131 (0.8%) 1 1/125 (0.8%) 1 1/15 (6.7%) 1
    Sensory loss 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Superficial siderosis of central nervous system 18/131 (13.7%) 23 4/125 (3.2%) 4 3/15 (20%) 4
    Syncope 3/131 (2.3%) 4 5/125 (4%) 6 0/15 (0%) 0
    Transient ischaemic attack 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Tremor 1/131 (0.8%) 1 1/125 (0.8%) 1 1/15 (6.7%) 1
    Trigeminal neuralgia 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Psychiatric disorders
    Abnormal dreams 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Adjustment disorder 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Agitation 0/131 (0%) 0 5/125 (4%) 5 1/15 (6.7%) 1
    Anxiety 7/131 (5.3%) 8 2/125 (1.6%) 2 1/15 (6.7%) 1
    Confusional state 3/131 (2.3%) 3 2/125 (1.6%) 2 0/15 (0%) 0
    Delusion 2/131 (1.5%) 2 2/125 (1.6%) 3 1/15 (6.7%) 1
    Depressed mood 0/131 (0%) 0 3/125 (2.4%) 3 0/15 (0%) 0
    Depression 6/131 (4.6%) 6 8/125 (6.4%) 8 1/15 (6.7%) 1
    Disinhibition 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Emotional disorder 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hallucination 1/131 (0.8%) 1 1/125 (0.8%) 1 1/15 (6.7%) 1
    Initial insomnia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Insomnia 1/131 (0.8%) 1 3/125 (2.4%) 3 0/15 (0%) 0
    Irritability 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Nightmare 2/131 (1.5%) 2 2/125 (1.6%) 2 0/15 (0%) 0
    Procedural anxiety 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Rapid eye movements sleep abnormal 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Suicidal ideation 0/131 (0%) 0 3/125 (2.4%) 5 0/15 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 2/131 (1.5%) 2 2/125 (1.6%) 2 0/15 (0%) 0
    Dysuria 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Glycosuria 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Haematuria 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hydronephrosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hypertonic bladder 0/131 (0%) 0 2/125 (1.6%) 2 0/15 (0%) 0
    Nephrolithiasis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Pollakiuria 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Renal cyst 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Renal failure 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Urge incontinence 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Urinary incontinence 3/131 (2.3%) 3 3/125 (2.4%) 3 0/15 (0%) 0
    Urinary retention 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Urinary tract obstruction 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/63 (1.6%) 1 1/61 (1.6%) 1 0/3 (0%) 0
    Uterine disorder 1/68 (1.5%) 1 0/64 (0%) 0 0/12 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Cough 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Dysphonia 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Dyspnoea 1/131 (0.8%) 1 3/125 (2.4%) 4 0/15 (0%) 0
    Dyspnoea exertional 1/131 (0.8%) 1 2/125 (1.6%) 2 0/15 (0%) 0
    Haemoptysis 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Hiccups 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Hypoxia 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Oropharyngeal pain 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Pharyngeal swelling 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Pleural effusion 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Productive cough 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Pulmonary mass 2/131 (1.5%) 2 0/125 (0%) 0 1/15 (6.7%) 1
    Rhinitis allergic 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Rhinorrhoea 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Sinus congestion 2/131 (1.5%) 2 0/125 (0%) 0 1/15 (6.7%) 1
    Sleep apnoea syndrome 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Upper-airway cough syndrome 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Skin and subcutaneous tissue disorders
    Actinic keratosis 1/131 (0.8%) 3 0/125 (0%) 0 1/15 (6.7%) 1
    Alopecia 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Angioedema 0/131 (0%) 0 1/125 (0.8%) 1 1/15 (6.7%) 1
    Dermatitis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Dermatitis allergic 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Dermatitis bullous 1/131 (0.8%) 5 0/125 (0%) 0 0/15 (0%) 0
    Dermatitis contact 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Ecchymosis 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Eczema 0/131 (0%) 0 1/125 (0.8%) 1 1/15 (6.7%) 1
    Erythema 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Ingrowing nail 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Lentigo 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Petechiae 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Precancerous skin lesion 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Pruritus 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Purpura 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Rash 0/131 (0%) 0 6/125 (4.8%) 8 2/15 (13.3%) 2
    Rash macular 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Seborrhoeic dermatitis 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Skin discolouration 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Skin hyperpigmentation 1/131 (0.8%) 2 0/125 (0%) 0 0/15 (0%) 0
    Skin hypopigmentation 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Skin lesion 0/131 (0%) 0 3/125 (2.4%) 3 0/15 (0%) 0
    Skin ulcer 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Transient acantholytic dermatosis 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Urticaria 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Surgical and medical procedures
    Blepharorrhaphy 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cancer surgery 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Cardiac pacemaker insertion 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Cardiac pacemaker replacement 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Cataract operation 3/131 (2.3%) 4 2/125 (1.6%) 3 1/15 (6.7%) 2
    Cryotherapy 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Dental implantation 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Endodontic procedure 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Intraocular lens implant 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Lens extraction 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Medical device removal 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Precancerous lesion excision 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Shoulder arthroplasty 0/131 (0%) 0 1/125 (0.8%) 1 1/15 (6.7%) 1
    Skin cryotherapy 1/131 (0.8%) 1 1/125 (0.8%) 1 0/15 (0%) 0
    Skin neoplasm excision 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Spinal operation 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Tooth extraction 1/131 (0.8%) 1 6/125 (4.8%) 6 0/15 (0%) 0
    Vertebroplasty 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Vitrectomy 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Vascular disorders
    Hot flush 3/131 (2.3%) 3 0/125 (0%) 0 0/15 (0%) 0
    Hypertension 3/131 (2.3%) 3 6/125 (4.8%) 6 0/15 (0%) 0
    Hypertensive urgency 0/131 (0%) 0 1/125 (0.8%) 1 0/15 (0%) 0
    Hypotension 4/131 (3.1%) 4 2/125 (1.6%) 2 0/15 (0%) 0
    Labile hypertension 0/131 (0%) 0 0/125 (0%) 0 1/15 (6.7%) 1
    Orthostatic hypotension 2/131 (1.5%) 2 0/125 (0%) 0 0/15 (0%) 0
    Peripheral venous disease 1/131 (0.8%) 1 0/125 (0%) 0 0/15 (0%) 0
    Poor venous access 3/131 (2.3%) 3 1/125 (0.8%) 1 0/15 (0%) 0

    Limitations/Caveats

    As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline. Thus, the arm was not utilized, and no data collected for outcomes; only safety data reported.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 30 days but less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03367403
    Other Study ID Numbers:
    • 16933
    • I5T-MC-AACG
    First Posted:
    Dec 8, 2017
    Last Update Posted:
    Feb 15, 2022
    Last Verified:
    Jan 1, 2022